This project is studying the regulation of HMG-CoA reductase, the major regulatory enzyme in cholesterol biosynthesis. We have demonstrated that phosphorylation of the enzyme is an early in vivo regulatory event, with either mevalonate feeding or cholesterol feeding. In addition, optimal assay conditions have been defined for homogeneous HMG-CoA reductase, which has been purified 12,700-fold from the microsomes of cholestyramine-treated rats.